The proposed research is concerned with the isolation and enrichment of lymphoid and myeloid cells during early stages of differentiation so as to define their antigenic determinants and determine the functions of these molecules in cellular differentiation and neoplasia. Ia-like antigens, potential precursor Ia-like molecules isolated from myeloid cells and antigens defined on leukemic myeloblasts by a non-human primate antiserum to "shed" acute myelogenous leukemia antigens will be characterized. Methods used to isolate and biochemically analyze the different antigens detected by the rabbit antisera to human Ia and monkey antiseum to myeloblast leukemia associated antigens will include internal and external radiolabelling of viable cells followed by detergent solubilization and partial purification of affinity columns. A central theme of this proposal will involve the characterization of a large molecular weight component which has been isolated from a precursor of conventional surface Ia-like antigens. The presence of the newly defined precursor Ia-like antigens and myeloblast leukemia associated antigens in various stages of normal lymphoid and myeloid differentiation as well as leukemic disorders will be determined by immunofluorescence (manual and fluorescence activated cell sorter), cytotoxicity and immunoprecipitation analysis. These studies will provide important clues to the heterogeneity which exists within human lymphoid and myeloid malignancies. Furthermore, such studies should allow better definition of the antigenic markers during early stages of normal lymphoid and myeloid differentiation as well as possible neo-antigens expressed during leukemogenesis.